Primary Central Nervous System Vasculitis: Analysis of 101 Patients Carlo Salvarani, MD, 1 Robert D. Brown, Jr, MD, 1 Kenneth T. Calamia, MD, 2 Teresa J. H. Christianson, BS, 3 Stephen D. Weigand, MS, 3 Dylan V. Miller, MD, 4 Caterina Giannini, MD, 4 James F. Meschia, MD, 5 John Huston III, MD, 6 and Gene G. Hunder, MD 7 Objective: To analyze the clinical findings, response to therapy, outcome, and incidence of primary central nervous system vasculitis (PCNSV) in a large cohort from a single center. Methods: We retrospectively studied 101 patients with PCNSV, selected by predetermined diagnostic criteria, who were seen during a 21-year period. This was a collaborative study by five departments at a large multispecialty clinic. Clinical findings and outcomes were compared among patients categorized by method of diagnosis, response to therapy, survival, and degree of disability. An annual incidence rate was calculated. Results: Seventy patients were diagnosed by angiography and 31 by central nervous system biopsy. Three histological patterns were observed during biopsy. Although most patients responded to therapy, an increased mortality rate was observed. Relapses occurred in one fourth of patients. Mortality rate and disability at last follow-up were greater in those who presented with a focal neurological deficit, cognitive impairment, cerebral infarctions, and angiographic large-vessel involvement but were lower in those with prominent gadolinium-enhanced lesions when evaluated by magnetic resonance imaging. The annual incidence rate of PCNSV was 2.4 cases per 1,000,000 person-years. Interpretation: PCNSV is a rare disease that may result in serious neurological outcomes or death. Angiography and brain biopsy may complement each other when determining the diagnosis. Early recognition and treatment may reduce poor out- comes. PCNSV is a variable syndrome that appears to consist of several subsets of heterogeneous diseases. Ann Neurol 2007;62:442– 451 Primary central nervous system vasculitis (PCNSV) is an uncommon and serious form of vasculitis that is limited to the brain and spinal cord. 1–9 In 1988, Ca- labrese and Mallek 5 suggested diagnostic criteria for PCNSV that included development of a neurological deficit unexplained by other processes, an angiogram with characteristic features of vasculitis, or a central nervous system (CNS) biopsy specimen showing vascu- litis. Because of the more invasive nature of CNS bi- opsy, angiography has become preferred for evaluating patients with suggestive symptoms. However, optimal angiographic criteria for the diagnosis of PCNSV have not been delineated, and the relative accuracy of an- giography when compared with biopsy remains uncer- tain. Angiographic changes typical of vasculitis may be seen in patients with normal brain biopsy findings or with other diseases. 9,10 Some investigators have found that cases diagnosed by angiography alone have a more benign form of the disease; such cases may also have findings that are difficult to distinguish from those of reversible cerebral vasoconstriction syndrome. 11–13 Be- cause of the lack of uniform diagnostic criteria and the relatively small numbers of patients in previous series, the clinical spectrum of PCNSV, its response to treat- ment, and its long-term outcome are still uncertain. In this study, we reviewed all cases of PCNSV seen at Mayo Clinic (Rochester, MN) from 1983 through 2003. Patients and Methods Identification of Patients We used our institution’s medical record diagnostic linkage system to identify all patients treated at Mayo Clinic (Roch- ester, MN) from January 1, 1983, through December 31, 2003, who had a diagnosis of vasculitis involving the CNS. We reviewed records of all patients with findings of vasculitis involving the CNS and excluded patients with findings con- sistent with other diagnoses (eg, polyarteritis nodosa, lupus From the 1 Department of Neurology, Mayo Clinic, Rochester, MN; 2 Division of Rheumatology, Mayo Clinic, Jacksonville, FL; Divi- sions of 3 Biostatistics and 4 Anatomic Pathology, Mayo Clinic, Rochester, MN; 5 Department of Neurology, Mayo Clinic, Jackson- ville, FL; and 6 Department of Radiology and 7 Division of Rheuma- tology, Mayo Clinic, Rochester, MN. Received Apr 27, 2007, and in revised form Jul 11. Accepted for publication Aug 3, 2007. Current address for Dr Salvarani: Unita Operativa di Reumatologia, Archispedale S. Maria Nueova, Reggio Emilia, Italy. Published online Oct 9, 2007 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ana.21226 Address correspondence to Dr Brown, Jr, Department of Neurol- ogy, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail: brown@mayo.edu 442 © 2007 American Neurological Association Published by Wiley-Liss, Inc., through Wiley Subscription Services